Radiation damage is a generic term for physical damage or injury caused in organisms by exposure to radiation such as X-ray and gamma ray. As a cause of radiation damage, irradiation, radioactive contamination, and the like are known. Radiation damage occurs as early radiation damage (acute radiation damage), which is radiation damage accompanied by acute phase symptoms that develops right after or within several months of exposure to radiation, or delayed radiation damage (late radiation damage), which is radiation damage that develops several years to several decades after exposure to radiation.
The higher the cell division activity, the higher the sensitivity of the cell to radiation, and the cell renewal system including, for example, hematopoietic organs is most susceptible to radiation. For example, in early radiation damage, exposure to 1 Gy (gray) or more causes symptoms called radiation sickness, which involves symptoms similar to hangover such as nausea, vomiting, and general malaise, in some people. Exposure to 1.5 Gy or more affects hematopoietic cells, which are most susceptible, and the cessation of leucocyte and platelet supply results in increased hemorrhage and reduced immunocompetence, and in severe cases individuals die within about 30 to 60 days. Also, in the skin, in which epithelial basal cells are highly susceptible, by exposure to 3 Gy or more, hair loss and temporary erythema occur, and by exposure to 7 to 8 Gy, blister forms, and by exposure to 10 Gy or more, ulcer is observed. By exposure to 5 Gy or more of radiation, stem cells in the small intestine are killed, leading to the cessation of absorptive cell supply. As a consequence, individuals develop diarrhea due to reduced absorption capacity, or bacterial infection, and in severe cases, die within 20 days. Exposure to an extremely high radiation dose of 15 Gy or more affects the central nerve, causing disturbed consciousness and symptoms of shock. The effect on the central nerve appears quickly, killing most of the irradiated individuals within five days. Meanwhile, in delayed radiation damage, the incidence rates of various types of malignant tumors including leukemia, radiation cataract, and the like are increased.
Currently, as a preventive measure against radiation exposure, prevention of uptake of radioactive substances generated under unusual circumstances such as accidents by, for example, administration of a stable isotope or a chelating agent corresponding to the radioactive substance, is mainly provided to thereby minimize the internal exposure. However, there is no preventive drug for inhibiting, for example, the development of cancer in those who are exposed to radiation on a daily basis such as cabin attendants and radiology technicians. Moreover, no preventive drug for inhibiting side effects in the patients undergoing cancer radiotherapy, who are exposed to a large dose of radiation, has been established yet. Further, as prevention of side effects of radiotherapy, administration of Shi Quan Da Bu Tang, a Chinese traditional medicine, is also known; however, this is not common. The former is intended to minimize radiation exposure per se by preventing the uptake of radioactive substances generated, whereas the latter is intended to inhibit the development of symptoms caused by radiation to which individuals are exposed. As a therapeutic method for radiation exposure, administration of a hematopoiesis-promoting cytokine and bone marrow transplantation are known. These methods are therapeutic methods for bone marrow suppression, which is one of the symptoms of radiation damage caused by the radioactive substances accumulated in the body, or by direct irradiation. Since bone marrow cells are rendered incapable of undergoing normal cell division by radiation damage, cytokines such as G-CSF are administered to the remaining normal cells to promote proliferation and differentiation of blood cells. In severer cases, transplantation of bone marrow cells may be performed.
In addition, as a preventive and/or therapeutic agent for radiation damage, nitroprusside (see Patent Document 1), lactoferrin (see Patent Document 2), 6,10,14,18-tetramethyl-5,9,13,17-nonadecatetraen-2-one (see Patent Document 3), a pyrazolone derivative (see Patent Document 4), the growth factors SCF, IL3, GM-CSF, and IL6 (see Patent Document 5), (±)-N,N′-propylenedinicotinamide (see Patent Document 6), 13-oxygermylpropionic acid (see Patent Document 7), β-lapachone (see Patent Document 8), a phosphorus derivative of alkaloid (see Patent Document 9), and α-D-glucopyranosyl-(1→2)-L-ascorbic acid (see Patent Document 10) have been proposed.
Meanwhile, 5-ALA is known as an intermediate of the tetrapyrrole biosynthetic pathway, which is widely present in animals, plants, and fungi. Normally, 5-ALA is biosynthesized by 5-aminolevulinate synthetase from succinyl CoA and glycine. Photodynamic therapy using 5-ALA (hereinbelow, may also be referred to as “ALA-PDT”) is also developed, which is attracting attention as a less invasive therapeutic method that can maintain QOL, and for example, a diagnostic and/or therapeutic agent for tumor prepared with ALA and the like has been reported. Further, 5-ALA is also known to be useful as a preventive or improving agent or a therapeutic agent for adult diseases, cancer, and male infertility (see for example, Patent Documents 11 to 13).